Molecular basis, physiopathology and treatment of neurodegenerative diseases



Research center

47 bld de l'Hôpital
75651 Paris
Alexis Brice


Université Pierre et Marie Curie
Université Pierre et Marie Curie


Phone: 01 57 27 46 82
Fax: 01 57 27 47 95
UMRS 1127 UMR 7225

Mots clefs

bases moléculaires
Démences fronto-temporales
Ataxies cérébelleuses
Paraplégies spastiques et dystonies


Depienne, C, et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet, 5:e1000381, 2009.
Mochel, F, et al. Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA). Brain, 132:801-9, 2009.

Benajiba, L, et al. TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann Neurol, 65:470-3, 2009.

Lesage, S, et al. Parkinson?s disease-related LRRK2 G2019S mutation results for independent mutational events in humans. HMG,19:1998-2004, 2010.

Slabicki, M, et al. A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic
paraplegia. PLOS-Biol, 8:e1000408, 2010.

Nalls, MA, et al. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet, 377:641-9, 2011.
Corvol, JC, et al. The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: a randomized crossover clinical trial. Ann Neurol, 69:111-8, 2011.

Depienne, C, et al. RAD51 haploisufficiency causes congenital mirror movements in humans. AJHG, 90:301-7, 2012.

Mochel, F, et al. Adult polyglucosan body disease: natural history and key MRI findings. Ann Neurol, 72:433-41, 2012.

Tesson, C, et al. Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spasticparaplegia. AJHG, 91:1051-64, 2012.

Lee, Y-C, Dürr, A, et al. Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann Neurol, 72:859-69, 2012.

Palminteri S, et al. Critical roles for anterior insula and dorsal striatum in punishment-based avoidance learning. Neuron, 76:998-1009,2012.

Martin, E, et al. Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia.AJHG, 92:238-44, 2013.

Chort, A, et al. Interferon-beta induces clearance of mutant ataxin-7 and improves locomotion in SCA7 knock-in mice. Brain,136:1732-45, 2013.

Depienne, C, et al. Brain white matter oedema due to ClC-2 chloride channel defi ciency: an observational analytical study. Lancet Neurol, 12:659-68, 2013.

Boukhris, A, et al. Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. AJHG. 93:118-23,2013.

Lesage, S, et al. G51D ?-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann Neurol, Mar 2013.

Bertolin, G, et al. Parkin interacts with the TOM machinery to modulate mitochondrial protein import. Autophagy, (in press), 2013.

Multiple-System Atrophy Research Collaboration. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med. 2013 Jul 18;369(3):233-44. doi: 10.1056/NEJMoa1212115. Epub 2013 Jun 12. Erratum in: N Engl J Med. 2014 Jul 3;371(1):94

van Rheenen W, et al. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat Genet. 2016 Sep;48(9):1043-8. doi: 10.1038/ng.3622. Epub 2016 Jul 25. .

Fields of research

Neurological and psychiatric diseases

Research Theme

The research is focused on molecular bases and physiopathology of different neurodegenerative disorders. The methods used are mapping and identification of susceptibility factors and genes responsible for these disorders (Parkinson's and Alzheimer's diseases, frontotemporal dementias, cerebellar ataxias and spastic paraplegias, dystonias). The Genetic progresses allow to establish the relative frequency of each gene, their mutational spectrum, phenotype-genotype correlations and to identify biomarkers thank to the biological material, including neuropathology and precise phenotypical data, collected throughout national and international networks.Physiopathological mechanisms are approached by characterization of cell and animal models (mice, drosophila and zebrafish) for different diseases (Parkinson's disease, cerebellar ataxias and spastic paraplegias). These models are used for elucidating physiopathological mechanisms, identifying modifier genes and for testing new therapeutical approaches.